Bz. Packard et al., MITOGENIC STIMULATION OF HUMAN-LYMPHOCYTES MEDIATED BY A CELL-SURFACEELASTASE, Biochimica et biophysica acta. Molecular cell research, 1269(1), 1995, pp. 51-56
A ca, 45-kDa protein which was recently identified and purified to hom
ogeneity from a solid tumor cell line as a T-cell mitogen was found to
have significant sequence similarities with human monocyte/neutrophil
elastase inhibitor (EI) [1]. Since EI is a known substrate for elasta
se, a determination of whether a cell surface expressed elastase-like
molecule might be the binding protein for this 45-kDa factor and media
te mitogenic signal transduction was undertaken. First, the surface of
tumor infiltrating lymphocytes, TIL 660. the indicator cell line used
for the purification of this mitogen, was shown to stain positively w
ith an anti-elastase antibody using flow cytofluorometry for quantitat
ion. Then, after observing an inverse correlation between cell surface
staining and the proliferative status of the TILs, behavior which mig
ht be expected of a growth factor receptor upon activation, mitogenic
signal transduction was attempted through the elastase-like molecules
of the lymphocytes' plasma membrane with the anti-elastase antibody in
the role of mitogen, A greater than 4-fold mitogenic stimulation was
observed when this antibody was covalently linked to latex beads; in c
ontrast, addition of the soluble form of the same antibody did not res
ult in any increase in [H-3]thymidine incorporation into the cells' DN
A. Hence, these data support induced clustering of an elastase-like mo
lecule on the lymphocyte surface as a mediator of mitogenesis and sugg
est that the binding protein for mitogenic signal transduction induced
by the 45-kDa protein, a member of the serine protease inhibitor (ser
pin) superfamily of proteins, is a molecule with structure similar to
a serine protease.